Implanted sensor processing system and method for processing implanted sensor output

ABSTRACT

A quantitative measurement system includes an external unit and an internal unit and is provided for obtaining quantitative analyte measurements, such as within the body. In one example application, the internal unit would be implanted either subcutaneously or otherwise within the body of a subject. The internal unit contains optoelectronics circuitry, a component of which may be comprised of a fluorescence sensing device. The optoelectronics circuitry obtains quantitative measurement information and modifies a load as a function of the obtained information. The load in turn varies the amount of current through coil, which is coupled to a coil of the external unit. A demodulator detects the current variations induced in the external coil by the internal coil coupled thereto, and applies the detected signal to processing circuitry, such as a pulse counter and computer interface, for processing the signal into computer-readable format for inputting to a computer.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/456,980, which was filed on Mar. 13, 2017, which is a continuation ofU.S. patent application Ser. No. 12/493,478, which was filed on Jun. 29,2009, abandoned, and is a divisional of U.S. patent application Ser. No.10/332,619, which was filed on Oct. 21, 2003, now U.S. Pat. No.7,553,280, and is a national stage application filed under 35 U.S.C. §371 of PCT/US01/20390, which was filed on Jun. 27, 2001, and is acontinuation-in-part of U.S. patent application Ser. No. 09/605,706,which was filed on Jun. 29, 2000, now U.S. Pat. No. 6,400,974, all ofwhich are incorporated by reference herein in their entireties.

BACKGROUND OF THE INVENTION Field of the Invention

This invention relates to a circuit and method for processing the outputof an implanted sensing device for detecting the presence orconcentration of an analyte in a liquid or gaseous medium, such as, forexample, the human body. More particularly, the invention relates to acircuit and method for processing the output of an implantedfluorescence sensor which indicates analyte concentration as a functionof the fluorescent intensity of a fluorescent indicator. The implantedfluorescence sensor is a passive device, and contains no power source.The processing circuit powers the sensor through inductively coupled RFenergy emitted by the processing circuit. The processing circuitreceives information from the implanted sensor as variations in the loadon the processing circuit.

Background Art

U.S. Pat. No. 5,517,313, the disclosure of which is incorporated hereinby reference, describes a fluorescence sensing device comprising alayered array of a fluorescent indicator molecule-containing matrix(hereafter “fluorescent matrix”), a high-pass filter and aphotodetector. In this device, a light source, preferably alight-emitting diode (“LED”), is located at least partially within theindicator material, such that incident light from the light sourcecauses the indicator molecules to fluoresce. The high-pass filter allowsemitted light to reach the photodetector, while filtering out scatteredincident light from the light source. An analyte is allowed to permeatethe fluorescent matrix, changing the fluorescent properties of theindicator material in proportion to the amount of analyte present. Thefluorescent emission is then detected and measured by the photodetector,thus providing a measure of the amount or concentration of analytepresent within the environment of interest.

One advantageous application of a sensor device of the type disclosed inthe '313 patent is to implant the device in the body, eithersubcutaneously or intravenously or otherwise, to allow instantaneousmeasurements of analytes to be taken at any desired time. For example,it is desirable to measure the concentration of oxygen in the blood ofpatients under anesthesia, or of glucose in the blood of diabeticpatients.

In order for the measurement information obtained to be used, it has tobe retrieved from the sensing device. Because of the size andaccessibility constraints on a sensor device implanted in the body,there are shortcomings associated with providing the sensing device withdata transmission circuitry and/or a power supply. Therefore, there is aneed in the art for an improved sensor device implanted in the body andsystem for retrieving data from the implanted sensor device.

SUMMARY OF THE INVENTION

In accordance with the present invention, an apparatus is provided forretrieving information from a sensor device, comprising an internalsensor unit for taking quantitative analyte measurements, including afirst coil forming part of a power supply for said sensor unit, a loadcoupled to said first coil, and a sensor circuit for modifying said loadin accordance with sensor measurement information obtained by saidsensor circuit; an external unit including a second coil which ismutually inductively coupled to said first coil upon said second coilcoming into a predetermined proximity distance from said first coil, anoscillator for driving said second coil to induce a charging current insaid first coil, and a detector for detecting variations in a load onsaid second coil induced by changes to said load in said internal sensorunit and for providing information signals corresponding to said loadchanges; and a processor for receiving and processing said informationsignals.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood with reference to thefollowing detailed description of a preferred embodiment in conjunctionwith the accompanying drawings, which are given by way of illustrationonly and thus are not limitative of the present invention, and wherein:

FIG. 1 is a block diagram of one preferred embodiment according to thepresent invention;

FIG. 2 is a schematic diagram of an internal sensor device unitaccording to one preferred embodiment of the invention;

FIGS. 3 and 4 are waveform diagrams illustrating signal waveforms atvarious points in the sensor device circuit;

FIGS. 5A-5E are diagrams of signals produced by the external datareceiving unit;

FIG. 6 is a schematic, section view of an implantable fluorescence-basedsensor according to the invention;

FIG. 7 is a schematic diagram of the fluorescence-based sensor shown inFIG. 6 illustrating the wave guide properties of the sensor;

FIG. 8 is a detailed view of the circled portion of FIG. 6 demonstratinginternal reflection within the body of the sensor and a preferredconstruction of the sensor/tissue interface layer;

FIG. 9 is a schematic diagram of an internal sensor device unitaccording to a second preferred embodiment of the invention; and

FIG. 10 is a timing diagram illustrating voltage levels of variousterminals of the comparator of FIG. 9 as the detector circuit cyclesthrough its operation.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

FIG. 1 shows a block diagram of one preferred embodiment of an implantedfluorescence sensor processing system according to the presentinvention.

The system includes an external unit 101 and an internal unit 102. Inone example of an application of the system, the internal unit 102 wouldbe implanted either subcutaneously or otherwise within the body of asubject. The internal unit contains optoelectronics circuitry 102 b, acomponent of which may be comprised of a fluorescence sensing device asdescribed more fully hereinafter with reference to FIGS. 6-8. Theoptoelectronics circuitry 102 b obtains quantitative measurementinformation and modifies a load 102 c as a function of the obtainedinformation. The load 102 c in turn varies the amount of current throughcoil 102 d, which is coupled to coil 101 f of the external unit. Anamplitude modulation (AM) demodulator 101 b detects the currentvariations induced in coil 101 f by coil 102 d coupled thereto, andapplies the detected signal to processing circuitry, such as a pulsecounter 101 c and computer interface 101 d, for processing the signalinto computer-readable format for inputting to a computer 101 e.

A variable RF oscillator 101 a provides an RF signal to coil 101 f,which in turn provides electromagnetic energy to coil 102 d, when thecoils 101 f and 102 d are within close enough proximity to each other toallow sufficient inductive coupling between the coils. The energy fromthe RF signal provides operating power for the internal unit 102 toobtain quantitative measurements, which are used to vary the load 102 cand in turn provide a load variation to the coil 101 f that is detectedby the external unit and decoded into information. The load variationsare coupled from the internal unit to the external unit through themutual coupling between the coils 101 f and 102 d. The loading can beimproved by tuning both the internal coil and the external coil toapproximately the same frequency, and increasing the Q factor of theresonant circuits by appropriate construction techniques. Because oftheir mutual coupling, a current change in one coil induces a current inthe other coil. The induced current is detected and decoded intocorresponding information.

RF oscillator 101 a drives coil 101 f, which induces a current in coil102 d. The induced current is rectified by a rectifier circuit 102 a andused to power the optoelectronics 102 b. Data is generated by theoptoelectronics in the form of a pulse train having a frequency varyingas a function of the intensity of light emitted by a fluorescencesensor, such as described in the aforementioned '313 patent. The pulsetrain modulates the load 102 c in a manner so as to temporarily shortthe rectifier output terminal to ground. This change in load causes acorresponding change in the current through the internal coil 102 d,thereby causing a change in the magnetic field surrounding external coil101 f. This change in magnetic field causes a proportional change in thevoltage across coil 101 f, which is observable as an amplitudemodulation. The following equation describes the voltage seen on theexternal coil:

V=I[Z+((ωM)²)/Zs]  (1)

where

-   -   V=voltage across the external coil    -   I=current in the external coil    -   Z=impedance of the primary coil    -   ω=frequency (rad/sec)    -   M=mutual inductance between the coils    -   Zs=impedance of the sensor equivalent circuit

As shown by equation (1), there is a direct relationship between thevoltage across the external coil and the impedance presented by theinternal sensor circuit. While the impedance Zs is a complex numberhaving both a real and imaginary part, which corresponds respectively tochanges in amplitude and frequency of the oscillation signal, the systemaccording to the present embodiment deals only with the real part of theinteraction. It will be recognized by those skilled in the art that bothtypes of interaction may be detected by appropriately modifying theexternal circuit, to improve the signal-to-noise ratio.

FIG. 2 shows a schematic diagram of one embodiment of an internal sensordevice unit according to the invention. The coil 102 d (L1) inconjunction with capacitor C1, diode D1 (rectifier 102 a) zener diode D2and capacitor C2 constitute a power supply for the internal unit 102.Current induced in coil L1 by the RF voltage applied to external coil101 f by oscillator 101 a (see FIG. 1) is resonated in the L-C tankformed by L1 and capacitor C1, rectified by diode D1, and filtered bycapacitor C2. Zener diode D2 is provided to prevent the voltage beingapplied to the circuit from exceeding a maximum value, such as 5 volts.As is known by those skilled in the art, if the voltage across capacitorC2 starts to exceed the reverse breakdown voltage of the zener diode D2,diode D2 will start to conduct in its reverse breakdown region,preventing the capacitor C2 from becoming overcharged with respect tothe maximum allowable voltage for the circuit.

Voltage regulator 205 receives the voltage from capacitor C2 andproduces a fixed output voltage V_(ref) to the noninverting input ofoperational amplifier 201. The output terminal of the operationalamplifier 201 is connected to a light-emitting diode (LED) 202 connectedin series with a feedback resistor R1. The inverting input terminal ofoperational amplifier 201 is supplied with the voltage across R1, tothereby regulate the current through LED 202 to V_(ref)/R1 (ignoringsmall bias current). Light emitted from LED 202 is incident on thesensor device (not shown) and causes the sensor device to emit light asa function of the amount of the particular analyte being monitored. Thelight from the sensor device impinges on the photosensitive resistor203, whose resistance changes as a function of the amount of lightincident thereon. Photoresistor 203 is connected in series with acapacitor C3, and the junction of the photoresistor and the capacitor C3is connected to the inverting input terminal of comparator 204. Theother end of photoresistor 203 is connected to the output terminal ofthe comparator 204 through a conductor V_(comp). The output of thecomparator 204 is also connected to a load capacitor C4 and a resistornetwork R2, R3 and R4. The comparator forms a variable resistanceoscillator, with switching points determined by the values of R2, R3 andR4. C3 is a charge-up capacitor, which determines the base frequency ofthe oscillator for a given light level. This frequency is given by

f=1/(1.38*Rphoto*C3)  (2)

Rphoto=R _(2fc)[10^(−γ log(a/2fc))]  (3)

Where

-   -   R_(2fc) (=24 kΩ) is the resistance of photoresistor 203 at 2        footcandles    -   γ(=0.8) is the sensitivity of the photoresistor    -   a=the incident light level in footcandles

Equation (3) can be inverted to determine the intensity of light for agiven photoresistance; in conjunction with equation (2), the lightintensity can be determined from frequency. Of course, the values givenabove are provided as examples only for purposes of explanation. Suchvalues are determined on the basis of the particular photoresistorgeometry and materials used.

The comparator 204 switches to a high output when Vtime=V/3, Vcomp=V,and Vtrip=2V/3. Capacitor C3 begins to charge with time constantRphoto*Ctime. When Vtime reaches 2V/3 the comparator switches states toa low output, changing Vcomp to Vcomp=0, and Vtrip to Vtrip=V/3. At thispoint C3 will discharge through Rphoto. Therefore a 50% duty cycle isestablished, with the frequency being determined by equation (2). Rphotovaries as a function of incident light, given by equation (3).

C4 is a load capacitor, which causes a voltage across C2 to decreasewhen the comparator switches states. C4 must be charged from 0V to Vdcwhen comparator 204 switches to a high output level state. The currentthrough C4 is supplied by C2, causing the voltage across C2 to decrease.This in turn causes current to flow through rectifier 102 a to begincharging capacitor C2, changing the instantaneous load on the tankcircuit including internal coil 102 d. This load is reflected into theimpedance of the external coil 101 f as given by equation (1).

The sensor operation for a single pulse is illustrated in FIG. 3.Channel 4 is the DC voltage on C2, channel 3 shows the same pulse on theexternal coil 101 f, and the output of the AM demodulator is shown atchannel 2. Channel 1 shows the output of a comparator which converts theAM demodulator output to a square wave capable of being processed by adigital counter. FIG. 4 shows two complete operation cycles, with thesame channel designations indicating the same points in the circuit.

The external unit 101 uses a microprocessor to implement the pulsecounter 101 c. When sufficient data has been received to obtain a validreading, the processor shuts down the RF oscillator. FIGS. 5A-5Eillustrate timing diagrams for a measurement reading. FIG. 5A shows theenvelope of the RF voltage signal applied to the external coil; FIG. 5Bshows the waveform of the internal power supply voltage; FIG. 5C shows awaveform of the intensity of LED 202; FIG. 5D shows the output of the AMdemodulator 101 b; and FIG. 5E shows the timing of the state of circuitoperations in accordance with the power supplied to the sensor unit. Theinternal unit power supply ramps up as the field strength increases.When the power supply output crosses the threshold voltage of the LEDplus the feedback voltage, the LED turns on. The AM demodulator outputcontains the measurement data and digital data in the form of ID codesand other parameters specific to the subject in which the internal unitis implanted. This data is encoded on the RF voltage signal through timedivision multiplexing of the optoelectronic output with digitalidentification and parameter storage circuits (not shown). The digitalcircuits use the RF voltage to generate appropriate clock signals.

The internal storage circuits can store ID codes and parametric valuessuch as calibration constants. This information is returned along witheach reading or quantitative measurement. The signals are clocked out byswitching from analog pulse train loading to digitally controlledloading at a predefined point in the measurement sequence. This point isdetected in the external unit by detecting a predefined bitsynchronization pattern in the output data stream. The ID number is usedto identify a particular subject and to prevent data corruption when twoor more subjects are in the vicinity of the external unit. Thecalibration factors are applied to the measurement information to obtainanalyte levels in clinical units.

A sensor 10 according to one aspect of the invention, which operatesbased on the fluorescence of fluorescent indicator molecules, is shownin FIG. 6. The sensor 10 is composed of a sensor body 12; a matrix layer14 coated over the exterior surface of the sensor body 12, withfluorescent indicator molecules 16 distributed throughout the layer; aradiation source 18, e.g. an LED, that emits radiation, includingradiation over a wavelength or range of wavelengths which interact withthe indicator molecules, i.e., in the case of a fluorescence-basedsensor, a wavelength or range of wavelengths which cause the indicatormolecules 16 to fluoresce; and a photosensitive element 20, e.g. aphotodetector, which, in the case of a fluorescence-based sensor, issensitive to fluorescent light emitted by the indicator molecules 16such that a signal is generated in response thereto that is indicativeof the level of fluorescence of the indicator molecules. The sensor 10further includes a module or housing 66 containing electronic circuitry,and a temperature sensor 64 for providing a temperature reading. In thesimplest embodiments, indicator molecules 16 could simply be coated onthe surface of the sensor body. In preferred embodiments, however, theindicator molecules are contained within the matrix layer 14, whichcomprises a biocompatible polymer matrix that is prepared according tomethods known in the art and coated on the surface of the sensor body.Suitable biocompatible matrix materials, which must be permeable to theanalyte, include methacrylates and hydrogels which advantageously can bemade selectively permeable to the analyte.

The sensor body 12 advantageously is formed from a suitable, opticallytransmissive polymer material which has a refractive index sufficientlydifferent from that of the medium in which the sensor will be used suchthat the polymer will act as an optical wave guide. Preferred materialsare acrylic polymers such as polymethylmethacrylate,polyhydroxypropylmethacrylate and the like, and polycarbonates such asthose sold under the trademark Lexan®. The material allows radiationgenerated by the radiation source 18 (e.g., light at an appropriatewavelength in embodiments in which the radiation source is an LED) and,in the case of a fluorescence-based embodiment, fluorescent lightemitted by the indicator molecules, to travel through it. Radiationsource or LED 18 corresponds to LED 202 shown in FIG. 2.

As shown in FIG. 7, radiation (e.g., light) is emitted by the radiationsource 18 and at least some of this radiation is reflected internally atthe surface of the sensor body 12, e.g., as at location 22, thereby“bouncing” back-and-forth throughout the interior of the sensor body 12.

It has been found that light reflected from the interface of the sensorbody and the surrounding medium is capable of interacting with indicatormolecules coated on the surface (whether coated directly thereon orcontained within a matrix), e.g., exciting fluorescence in fluorescentindicator molecules coated on the surface. In addition, light whichstrikes the interface at angles (measured relative to a direction normalto the interface) too small to be reflected passes through the interfaceand also excites fluorescence in fluorescent indicator molecules. Othermodes of interaction between the light (or other radiation) and theinterface and the indicator molecules have also been found to be usefuldepending on the construction of and application for the sensor. Suchother modes include evanescent excitation and surface plasma resonancetype excitation.

As demonstrated by FIG. 8, at least some of the light emitted by thefluorescent indicator molecules 16 enters the sensor body 12, eitherdirectly or after being reflected by the outermost surface (with respectto the sensor body 12) of the matrix layer 14, as illustrated in region30. Such fluorescent light 28 is then reflected internally throughoutthe sensor body 12, much like the radiation emitted by the radiationsource 18 is, and, like the radiation emitted by the radiation source,some will strike the interface between the sensor body and thesurrounding medium at angles too small to be reflected and will passback out of the sensor body.

As further illustrated in FIG. 6, the sensor 10 may also includereflective coatings 32 formed on the ends of the sensor body 12, betweenthe exterior surface of the sensor body and the matrix layer 14, tomaximize or enhance the internal reflection of the radiation and/orlight emitted by fluorescent indicator molecules. The reflectivecoatings may be formed, for example, from paint or from a metallizedmaterial.

An optical filter 34 preferably is provided on the light-sensitivesurface of the photodetector 20, which is manufactured of aphotosensitive material. Photodetector 20 corresponds to photodetector203 shown in FIG. 2. Filter 34, as is known from the prior art, preventsor substantially reduces the amount of radiation generated by the source18 from impinging on the photosensitive surface of the photosensitiveelement 20. At the same time, the filter allows fluorescent lightemitted by fluorescent indicator molecules to pass through it to strikethe photosensitive region of the detector. This significantly reduces“noise” in the photodetector signal that is attributable to incidentradiation from the source 18.

The application for which the sensor 10 according to one aspect of theinvention was developed in particular—although by no means the onlyapplication for which it is suitable—is measuring various biologicalanalytes in the human body, e.g., glucose, oxygen, toxins,pharmaceuticals or other drugs, hormones, and other metabolic analytes.The specific composition of the matrix layer 14 and the indicatormolecules 16 may vary depending on the particular analyte the sensor isto be used to detect and/or where the sensor is to be used to detect theanalyte (i.e., in the blood or in subcutaneous tissues). Two constantrequirements, however, are that the matrix layer 14 facilitate exposureof the indicator molecules to the analyte and that the opticalcharacteristics of the indicator molecules (e.g., the level offluorescence of fluorescent indicator molecules) are a function of theconcentration of the specific analyte to which the indicator moleculesare exposed.

To facilitate use in-situ in the human body, the sensor 10 is formed,preferably, in a smooth, oblong or rounded shape. Advantageously, it hasthe approximate size and shape of a bean or a pharmaceutical gelatincapsule, i.e., it is on the order of approximately 300-500 microns toapproximately 0.5 inch in length L and on the order of approximately 300microns to approximately 0.3 inch in depth D, with generally smooth,rounded surfaces throughout. The device of course could be larger orsmaller depending on the materials used and upon the intended uses ofthe device. This configuration permits the sensor 10 to be implantedinto the human body, i.e., dermally or into underlying tissues(including into organs or blood vessels) without the sensor interferingwith essential bodily functions or causing excessive pain or discomfort.

Moreover, it will be appreciated that any implant placed within thehuman (or any other animal's) body—even an implant that is comprised of“biocompatible” materials—will cause, to some extent, a “foreign bodyresponse” within the organism into which the implant is inserted, simplyby virtue of the fact that the implant presents a stimulus. In the caseof a sensor 10 that is implanted within the human body, the “foreignbody response” is most often fibrotic encapsulation, i.e., the formationof scar tissue. Glucose—a primary analyte which sensors according to theinvention are expected to be used to detect—may have its rate ofdiffusion or transport hindered by such fibrotic encapsulation. Evenmolecular oxygen (O2), which is very small, may have its rate ofdiffusion or transport hindered by such fibrotic encapsulation as well.This is simply because the cells forming the fibrotic encapsulation(scar tissue) can be quite dense in nature or have metaboliccharacteristics different from that of normal tissue.

To overcome this potential hindrance to or delay in exposing theindicator molecules to biological analytes, two primary approaches arecontemplated. According to one approach, which is perhaps the simplestapproach, a sensor/tissue interface layer—overlying the surface of thesensor body 12 and/or the indicator molecules themselves when theindicator molecules are immobilized directly on the surface of thesensor body, or overlying the surface of the matrix layer 14 when theindicator molecules are contained therein—is prepared from a materialwhich causes little or acceptable levels of fibrotic encapsulation toform. Two examples of such materials described in the literature ashaving this characteristic are Preclude™ Periocardial Membrane,available from W.L. Gore, and polyisobutylene covalently combined withhydrophiles as described in Kennedy, “Tailoring Polymers for BiologicalUses,” Chemtech, February 1994, pp. 24-31.

Alternatively, a sensor/tissue interface layer that is composed ofseveral layers of specialized biocompatible materials can be providedover the sensor. As shown in FIG. 8, for example, the sensor/tissueinterface layer 36 may include three sublayers 36 a, 36 b, and 36 c. Thesublayer 36 a, a layer which promotes tissue ingrowth, preferably ismade from a biocompatible material that permits the penetration ofcapillaries 37 into it, even as fibrotic cells 39 (scar tissue)accumulate on it. Gore-Tex® Vascular Graft material (ePTFE), Dacron®(PET) Vascular Graft materials which have been in use for many years,and MEDPOR Biomaterial produced from high-density polyethylene(available from POREX Surgical Inc.) are examples of materials whosebasic composition, pore size, and pore architecture promote tissue andvascular ingrowth into the tissue ingrowth layer.

The sublayer 36 b, on the other hand, preferably is a biocompatiblelayer with a pore size (less than 5 micrometers) that is significantlysmaller than the pore size of the tissue ingrowth sublayer 36 a so as toprevent tissue ingrowth. A presently preferred material from which thesublayer 36 b is to be made is the Preclude Periocardial Membrane(formerly called GORE-TEX Surgical Membrane), available from W.L. Gore,Inc., which consists of expanded polytetra-fluoroethylene (ePTFE).

The third sublayer 36 c acts as a molecular sieve, i.e., it provides amolecular weight cut-off function, excluding molecules such asimmunoglobulins, proteins, and glycoproteins while allowing the analyteor analytes of interest to pass through it to the indicator molecules(either coated directly on the sensor body 12 or immobilized within amatrix layer 14). Many well known cellulose-type membranes, e.g., of thesort used in kidney dialysis filtration cartridges, may be used for themolecular weight cut-off layer 36 c.

As will be recognized, the sensor as shown in FIG. 6 is whollyself-contained such that no electrical leads extend into or out of thesensor body, either to supply power to the sensor (e.g., for driving thesource 18) or to transmit signals from the sensor. All of theelectronics illustrated in FIG. 2 may be housed in a module 66 as shownin FIG. 6.

A second preferred embodiment of the invention is shown in FIG. 9, inwhich two detectors are employed, a signal channel detector 901 and areference channel detector 902. In the first embodiment as shown in FIG.2, a single detector 203 is used to detect radiation from thefluorescent indicator sensor device. While this system works well, it ispossible that various disturbances to the system will occur that mayaffect the accuracy of the sensor output as originally calibrated.

Examples of such disturbances include: changes or drift in the componentoperation intrinsic to the sensor make-up; environmental conditionsexternal to the sensor; or combinations thereof. Internal variables maybe introduced by, among other things: aging of the sensor's radiationsource; changes affecting the performance or sensitivity of thephotosensitive element; deterioration of the indicator molecules;changes in the radiation transmissivity of the sensor body, of theindicator matrix layer, etc.; and changes in other sensor components;etc. In other examples, the optical reference channel could also be usedto compensate or correct for environmental factors (e.g., factorsexternal to the sensor) which could affect the optical characteristicsor apparent optical characteristics of the indicator moleculeirrespective of the presence or concentration of the analyte. In thisregard, exemplary external factors could include, among other things:the temperature level; the pH level; the ambient light present; thereflectivity or the turbidity of the medium that the sensor is appliedin; etc. The optical reference channel can be used to compensate forsuch variations in the operating conditions of the sensor. The referencechannel is identical to the signal channel in all respects except thatthe reference channel is not responsive to the analyte being measured.

Use of reference channels in optical measurement is generally known inthe art. For example, U.S. Pat. No. 3,612,866, the entire disclosure ofwhich is incorporated herein by reference, describes a fluorescentoxygen sensor having a reference channel containing the same indicatorchemistry as the measuring channel, except that the reference channel iscoated with varnish to render it impermeable to oxygen.

U.S. Pat. Nos. 4,861,727 and 5,190,729, the entire disclosures of whichare incorporated herein by reference, describe oxygen sensors employingtwo different lanthanide-based indicator chemistries that emit at twodifferent wavelengths, a terbium-based indicator being quenched byoxygen and a europium-based indicator being largely unaffected byoxygen. U.S. Pat. No. 5,094,959, the entire disclosure of which is alsoincorporated herein by reference, describes an oxygen sensor in which asingle indicator molecule is irradiated at a certain wavelength and thefluorescence emitted by the molecule is measured over two differentemission spectra having two different sensitivities to oxygen.Specifically, the emission spectra which is less sensitive to oxygen isused as a reference to ratio the two emission intensities. U.S. Pat.Nos. 5,462,880 and 5,728,422, the entire disclosures of which are alsoincorporated herein by reference, describe a ratiometric fluorescenceoxygen sensing method employing a reference molecule that issubstantially unaffected by oxygen and has a photodecomposition ratesimilar to the indicator molecule. Additionally, Muller, B., et al.,ANALYST, Vol. 121, pp. 339-343 (March 1996), the entire disclosure ofwhich is incorporated herein by reference, describes a fluorescencesensor for dissolved CO₂, in which a blue LED light source is directedthrough a fiber optic coupler to an indicator channel and to a separatereference photodetector which detects changes in the LED lightintensity.

In addition, U.S. Pat. No. 4,580,059, the entire disclosure of which isincorporated herein by reference, describes a fluorescent-based sensorcontaining a reference light measuring cell for measuring changes in theintensity of the excitation light source—see, e.g., column 10, lines 1,et seq.

As shown in FIG. 9, the signal and reference channel detectors areback-to-back photodiodes 901 and 902. While photodiodes are shown, manyother types of photodetectors also could be used, such asphotoresistors, phototransistors, and the like. LED 903 corresponds tolight source 202 in FIG. 2. In operation, comparator 904 is set totrigger at ⅓ and ⅔ of the supply voltage Vss, as biased by resistors905, 906, and 907. The trigger voltages for comparator 904 could bemodified, if desired, by changing the values of the resistors. CapacitorC2 is a timing element, the value of which is adjusted for the magnitudeof the signal and reference channels. The current through eachphotodiode is a function of the intensity or power of incident lightentering it, as represented by the equation I=RP, where

I=current

R=responsivity (Amp/Watt) and

P=light power in watts.

In the fluorescence embodiment, the incident light power impinging uponthe photodiode detectors changes with analyte concentration.

FIG. 10 is a timing diagram showing the voltage levels of the terminals904 a, 904 b, and 904 c of the comparator 904. At the cycle start, thevoltage level of output terminal 904 c is at ground (low output state),the voltage level of capacitor C2 (which corresponds to the voltagelevel at input terminal 904 b) is at ⅔ Vss, and the voltage level ofinput terminal 904 a is at ⅓ Vss. In this instance, photodiode 901 isforward-biased and photodiode 902 is reverse-biased. The voltage dropacross the forward-biased photodiode 901 is simply its thresholdvoltage, while the reverse-biased photodiode 902 exhibits a current flowproportional to the incident light impinging upon it. This currentdischarges the capacitor C2 at a rate of dV/dt=I902/C2, until it reachesa voltage level of ⅓ Vss as shown in FIG. 10. Inserting the aboveequation for photodiode current results in the equation dV/dt=RP/C2.Solving for P, P=(dV*C2)/(dt*R), where

dV=difference between comparator trigger points (in the example ⅓ Vss)

C2=value of capacitor C2 in farads

dt=time to charge or discharge (as measured by the external unit) and

R=responsivity (in amps/watts) of the photodetector

At this time, the comparator 904 switches to a high output state Vss onoutput terminal 904 c. The trigger point (input terminal 904 a) is nowat ⅔ Vss, and the polarity of the photodiodes 901 and 902 is nowreversed. That is, photodiode 901 is now reverse-biased and photodiode902 is now forward-biased.

Photodiode 901 now controls the charging of capacitor C2 at a rate ofdV/dt=I901/C2 until the voltage of capacitor C2 reaches ⅔ Vss. When thevoltage across capacitor C2 reaches ⅔ Vss, the output of the comparator904 again switches to the low output state. So long as the system ispowered and incident light is present on the photodiodes, the cycle willcontinue to repeat as shown in FIG. 10.

If the incident light intensity on each photodiode detector 901 and 902is equal, then the comparator output will be a 50% duty cycle. If theincident light on each photodiode detector is not equal, then thecapacitor charge current will be different than the capacitor dischargecurrent. This is the case shown in FIG. 10, wherein the capacitor chargecurrent is higher than the capacitor discharge current. Because the samecapacitor is charged and discharged, the different charge and dischargetimes are a function only of the difference between the incident lightlevels on the two photodiode detectors. Consequently, the duty cycle ofthe squarewave produced by the comparator 904 is indicative of changesbetween incident light on the signal channel photodiode and incidentlight on the reference channel photodiode. Suitable algorithms fortaking into account changes in duty cycle of the squarewave from thecomparator in determining analyte concentration are generally known inthe art (see prior art references discussed supra) and will not befurther discussed herein.

Once the squarewave is established, it must be transferred to theexternal unit. This is done by loading the internal coil 908, and thendetecting the change in load on the external coil inductively coupled tothe internal coil. The loading is provided by resistor 910, which isconnected to the output terminal 904 c of the comparator 904. When thecomparator is in a high output state, an additional current Vss/R910 isdrawn from the voltage regulator 909. When the comparator is in a lowoutput state, this additional current is not present. Consequently,resistor 910 acts as a load that is switched into and out of the circuitat a rate determined by the concentration of analyte and the output ofthe reference channel. Because the current through resistor 910 isprovided by the internal tuned tank circuit including coil 908, theswitching of the resistor load also switches the load on the tankincluding internal coil 908. The change in impedance of the tank causedby the changing load is detected by a corresponding change in load onthe inductively coupled external coil, as described above. The voltageregulator 909 removes any effects caused by coil placement in the field.The LED 903 emits the excitation light for the indicator moleculesensor. Power for the LED 903 is provided by the voltage regulator. Itis important to keep the intensity of the LED constant during an analytemeasurement reading. Once the output of the voltage regulator is inregulation, the LED intensity will be constant. The step recovery timeof the regulator is very fast, with the transition between loadingstates being rapid enough to permit differentiation and AC coupling inthe external unit.

As also will be recognized, the fluorescence-based sensor embodimentsdescribed in FIGS. 6-8 are just examples to which the disclosedinvention may be applied. The present invention may also be applied in anumber of other applications such as, for example, an absorbance-basedsensor or a refractive-index-based sensor as described in U.S. patentapplication Ser. No. 09/383,148, filed Aug. 28, 1999, incorporatedherein by reference.

The invention having been thus described, it will be apparent to thoseskilled in the art that the same may be varied in many ways withoutdeparting from the spirit and scope of the invention. For example, whilethe invention has been described with reference to an analog circuit,the principles of the invention may be carried out equivalently throughthe use of an appropriately programmed digital signal processor. Any andall such modifications are intended to be encompassed by the followingclaims.

What is claimed is:
 1. A system comprising: a sensor unit for takingquantitative analyte measurements, the sensor unit including a firstinductor forming part of a power supply for said sensor unit, a loadcoupled to said first inductor, and a sensor circuit for modifying saidload in accordance with sensor measurement information obtained by saidsensor circuit; a reader including a second inductor that is mutuallyinductively coupled to said first inductor upon said second inductorbeing placed within a predetermined proximal distance from said firstinductor, a driver for driving said second inductor to induce a chargingcurrent in said first inductor, a detector for detecting variations in aload on said second inductor induced by changes to said load in saidsensor unit and for providing information signals corresponding to saidload changes, and a processor for receiving and processing saidinformation signals.
 2. The system of claim 1, wherein said sensorcircuit comprises an indicator that emits radiation in proportion tolevels of said analyte.
 3. The system of claim 2, wherein said loadcomprises a photosensitive resistor that receives radiation from saidindicator.
 4. The system of claim 2, wherein said sensor circuit furthercomprises a radiation source configured to emit electromagneticradiation that stimulates emission of the radiation.
 5. The system ofclaim 2, wherein said indicator emits fluorescent radiation inproportion to levels of said analyte.
 6. The system of claim 5, whereinsaid load comprises a photosensitive resistor that receives fluorescentradiation from said indicator.
 7. The system of claim 4, wherein saidradiation source for emitting electromagnetic radiation stimulatesemission of fluorescent radiation.
 8. The system of claim 1, whereinsaid sensor unit is implantable in the body of a mammal.
 9. The systemof claim 1, wherein said power supply further includes a chargingcapacitor that is charged by said charging current.
 10. The system ofclaim 1, wherein said detector of said reader includes an amplitudemodulation (AM) demodulator for detecting changes in amplitude of avoltage waveform caused by changes in said load, said voltage waveformbeing inductively reflected into said second inductor through said firstinductor.
 11. The system of claim 10, wherein said processor includes apulse counter for converting said detected changes in waveform amplitudeinto pulses suitable for being converted into computer-readable form.12. The system of claim 1, wherein said reader includes a computerconfigured to receive the processed information signals.
 13. The systemof claim 1, wherein said sensor circuit comprises an indicator thatabsorbs radiation in proportion to levels of said analyte.
 14. Thesystem of claim 1, wherein the sensor unit is an internal sensor unit.15. The system of claim 14, wherein the internal sensor unit is apartially or fully internal sensor unit.
 16. The system of claim 1,wherein the driver comprises an oscillator.
 17. A sensor device fordetecting the presence or concentration of an analyte in a medium,comprising: a sensor body; an indicator having a characteristic that isaffected by the presence or concentration of an analyte; a detectorconfigured to detect a signal from said indicator, said signal beingindicative of the characteristic of the indicator; and a first inductorcoupled to said detector, said first inductor being adapted to receivefrom a second inductor a magnetically induced electric current, andbeing further adapted to induce in said second inductor an electriccurrent that changes as a function of the signal detected by saiddetector.
 18. The sensor device of claim 17, further comprising aradiation source in said sensor body, wherein the radiation source isconfigured to emit radiation within said sensor body.
 19. The sensordevice of claim 18, wherein the indicator is positioned on said sensorbody to receive radiation emitted by said radiation source.
 20. Thesensor device of claim 18, wherein said characteristic is an opticalcharacteristic, and the detector comprises a photosensitive elementconfigured to receive light emitted by said indicator.
 21. The sensordevice of claim 17, wherein magnetically induced electric currentsupplies power to the sensor device.
 22. The sensor device of claim 17,wherein the sensor body is an enclosed sensor body and has an outersurface surrounding said sensor body.
 23. The sensor device of claim 17,wherein the detector is located in the sensor body.
 24. The sensordevice of claim 17, wherein the first inductor is located in the sensorbody.
 25. The sensor device of claim 17, wherein the indicator comprisesa matrix layer on the exterior surface of the sensor body, and indicatormolecules are distributed throughout the matrix layer.